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Acid‐catalysed hydrolysis of methoxy‐substituted trityl trifluoroethyl ethers: a kinetic and computational investigation of leaving group effects
Author(s) -
López Moisés Canle,
Demirtas Ibrahim,
Maskill Howard,
Mishima Masaaki
Publication year - 2008
Publication title -
journal of physical organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.325
H-Index - 66
eISSN - 1099-1395
pISSN - 0894-3230
DOI - 10.1002/poc.1332
Subject(s) - chemistry , protonation , conjugate acid , heterolysis , reaction rate constant , hydrolysis , medicinal chemistry , dissociation (chemistry) , ether , acid dissociation constant , reactivity (psychology) , dissociation constant , ion , kinetics , aqueous solution , catalysis , organic chemistry , medicine , biochemistry , physics , alternative medicine , receptor , pathology , quantum mechanics
Trityl trifluoroethyl (TFE) ether and its 4‐methoxy, 4,4′‐dimethoxy‐, and 4,4′,4″‐trimethoxy‐substituted analogues have been prepared; the dimethoxy and trimethoxy compounds undergo ready acid‐catalysed hydrolysis at constant ionic strength = 1 mol dm −3 at 25°C. The monomethoxy compound is less reactive and the parent trityl analogue showed minimal reactivity. Using presently reported and literature kinetics results with p K a values of protonated substrates, first‐order rate constants covering 12 orders of magnitude have been determined for heterolysis/dissociation of 11 protonated dimethoxytrityl derivatives DMTrYH + where YH = H 2 O, CF 3 CH 2 OH, ArNH 2 and RNH 2 . There is a good correlation between logarithms of these rate constants and the p K a values of the conjugate acids (Y ${H}_{2}^{+}$ ) of the nucleofuges YH. Enthalpies and corresponding free energies at 25°C for the dissociation of the specifically solvated ions CH 3 ${---}{\rm YH}({H}_{2} {O})_{n}^{+}$ (YH = MeOH and CF 3 CH 2 OH, n = 1; H 2 O, n = 2; and NH 3 , n = 3) have been calculated at the B3LYP/6‐31+G* level. Corresponding gas phase calculations have also been carried out for Ph 3 C ${---}{\rm YH}({H}_{2} {O})_n^+$ (YH = H 2 O, n = 2; MeOH, n = 1; CF 3 CH 2 OH, n = 1 and NH 3 , n = 3) and, in addition, structures for these solvated ions with (YH = H 2 O, MeOH and NH 3 ) have been calculated. The specifically solvated ion Ph 3 C ${---}$ O(H)CH 2 CF 3 (H 2 O) + does not correspond to a stable bonded species in the gas phase, which suggests that acid‐catalysed fragmentation of methoxy‐substituted analogues of Ph 3 C ${---}$ OCH 2 CF 3 in aqueous solution are concerted with proton transfer in which case the hydrolytic cleavage will be general acid catalysed. Copyright © 2008 John Wiley & Sons, Ltd.